This invention relates to the enantioselective reduction of prochiral ketones using a borane reducing agent in the presence of a novel and valuable chiral oxazaborolidine catalyst and to certain of said chiral oxazaborolidine catalysts useful in said reduction.
The enantioselective reduction of prochiral ketones to yield substantially enantiomerically pure alcohols has long been a goal of synthetic organic chemists. A number of reagents have been reported which effect such a transformation. (See, for example, Corey, U.S. Pat. No. 4,943,635, the subject matter of which is incorporated herein by reference). However, these methods suffer from one or more of the following drawbacks: (a) unacceptable amounts of the undesired enantiomer present as an impurity with the product; (b) low yields of alcohol; (c) difficulty of carrying out the reaction; (d) expense of preparing the catalyst; (e) difficulty in preparing the catalyst; or (f) inapplicability to a wide range of substituted prochiral ketones.
In Corey, supra, and Merck, European Patent Application Nos. 0 453 288 A1 and 0 453 298 A2, enantioselectively effective oxazaborolidine catalysts are disubstituted at the C.sub.5 carbon atom of formula (I) below. When said carbon atom is not disubstituted, the degree of enantioselection has been reported to be much lower (see Martens, et al., Tetrahedron:Asymmetry, 3, 347-50 (1992)).
In copending application PCT/US93/00687, it is disclosed that cis diphenyl substituted oxazaborolidines are useful catalysts for the enantioselective reduction of prochiral ketones to optically active alcohols. Disubstitution at the C.sub.5 carbon atom was shown therein to be unnecessary. To obtain high enantiomeric excess in the reduction of prochiral ketones it is of primary importance that one face of the oxazaborolidine catalyst is completely blocked.
It is therefore an object of this invention to provide cis dialkyl, cis C-4 alkyl, C-5 phenyl and cis C-4 phenyl, C-5 alkyl substituted chiral oxazaborolidine compounds which are capable of directing the enantioselective reduction of prochiral ketones to generate substantially enantiomerically pure alcohols.
It is a further object of this invention to provide said chiral oxazaborolidine compounds which are easily prepared from relatively inexpensive starting materials or readily available starting materials.
It is a still further object of this invention to provide a method of using said chiral oxazaborolidine compounds as catalysts for the enantioselective reduction of prochiral ketones to afford substantially enantiomerically pure alcohols.